We propose to evaluate the neurohumoral control of ion transport in intestinal and colonic epithelium. The effect of several bioactive amines, polypeptides and opioid-like peptides on ion transport will be studied. We plan to determine the action of these various agonists on 1) ion transport in vitro (as measured by transmural fluxes across sheets of mucosa and uptake by and efflux from isolated epithelial cells) as well as 2) their binding to receptors on these epithelial cells; and 3) their ability to alter mucosal cyclic AMP. We will extend our present preliminary findings that 1) the colon possesses both alpha and beta adrenergic receptors; 2) opiate receptors are present on small intestinal and colonic epithelial cells and opiate alkaloids and opioid-like peptides have a direct effect on ion transport in the intestine; and 3) somatostatin inhibits ion secretion and may have a role in the control of diarrhea associated with various endocrine tumors. We will also explore the role of calcium as the mechanism by which various agents affect ion transport. These studies should provide increased understanding of the control of intestinal ion transport and the mechanism by which several agonists induce active ion secretion.